DESCRIPTION (provided by candidate): This proposed 5 year development period will be used for research and training activities that will give Dr. Fox the skills to become an independent investigator. Dr. Fox's long-term career goals are: 1) to develop expertise in evaluating large clinical datasets; 2) to generate analyses of the impact of HIV treatment programs; and 3) to develop novel analytic approaches to estimating the impact of HIV programs on clinical and social outcomes. This training will include formal class study, carrying out a research project, and research mentorship from experts in HIV, epidemiology and mathematical modeling. The training will focus on: 1) a thorough understanding HIV management; 2) specialized epidemiologic methods; and 3) practical research implementation skills. The primary research project is a study of drop-outs from one of the largest HIV treatment sites in Africa (more than 11,000 patients on antiretroviral therapy), the Themba Lethu Clinic (TLC) in Johannesburg, South Africa. Despite the large scale roll-out of antiretroviral therapy (ART) in 2004 in South Africa, many patients who test HIV-positive never start ART and many who start drop out of care. Information on where in the continuum of care patients are being lost is of vital importance to the success of ART programs. The aims of this study are: 1): to measure the rates and predictors of losses from TLC; 2) to validate TLC mortality data using South Africa's National Death Registry; 3) to estimate the effectiveness of ART on mortality; and 4) to estimate the impact of strategies to increase retention on mortality using mathematical modeling. We will conduct a longitudinal cohort study (built on the TLC cohort run by co-mentor Sanne) assessing drop out rates among patients in 3 populations: 1) patients testing HIV-positive; 2) patients initiating pre-ART HIV care; and 3) patients on ART. The Therapy Edge(tm) database which is currently being used at TLC will be used to monitor groups 2 and 3. We will enroll subjects in group 1 and will use the database to assess drop-outs from each population. We will conduct a validation study of mortality data for all patients lost to follow-up, and use validated data to assess the effectiveness of ART comparing pre-ART and ART mortality rates using marginal structural models. RELEVANCE: To best utilize resources for maintaining patients in HIV care, detailed information is needed on when patients are lost, how we can identify them and what can be done to increase retention. The results of this study will give a complete picture of drop out and mortality from HIV care, what effect treatment programs are having on mortality, and where limited resources for retaining patients could have the greatest impact.